Synthesis of Diastereomeric 8‐Fluoro‐ABC‐Steroid Building Blocks

An eight‐step linear sequence for the preparation of two diastereomers of an 8‐fluoro‐ABC‐steroid building block was developed. Key step was an intramolecular Diels–Alder reaction of an intermediate o‐quinodimethane formed from a benzocyclobutene substituted with a 5‐fluorohex‐5‐en‐4‐one chain. This side chain was prepared from 6‐chlorohex‐1‐ene by bromofluorination, elimination of HBr, Finkelstein reaction and alkylation of a literature‐known benzocyclobutene derivative with the thus‐formed 6‐iodo‐2‐fluorohex‐1‐ene. Allylic oxidation of side chain's fluorovinyl moiety to an α‐fluoro‐α,β‐unsaturated ketone completed the preparation of the precursor for the [4+2]‐cycloaddition. Two diastereomeric ABC‐building blocks for hitherto widely unknown steroids with a fluorine substituent in 8‐position were prepared in a convergent synthesis with eight linear steps from 6‐chlorohex‐1‐ene and a benzocyclobutene derivative. Key step was an intramolecular Diels–Alder reaction of an o‐quinodimethane with a fluorine‐containing α,β‐unsaturated ketone.